Genetic variations and their impact on protein function: Study on deleterious nsSNPs in Cancer related genes of Wnt pathway

Publication date: Available online 31 October 2019Source: Meta GeneAuthor(s): Swetha Sunkar, Madineni Aravind, S. Surya Chandan Reddy, Desam NeeharikaAbstractCancer is a deadly disease caused by several factors such as variations in genes that influence cell growth and division. Wnt pathway is commonly involved in controlling gene expression and cellular behavior in many types of cancer. Our study focused on cancer related novel gene candidates namely DKK3, SFRP2, SFRP4 and SFRP5 involved in Wnt pathway (Wingless integrated pathway) to analyze the potentially deleterious non-synonymous single nucleotide polymorphisms. From the dbSNP database, the nsSNPs of genes were retrieved and analyzed for their pathogenicity using various computational tools such as PolyPhen-2.0, FATHMM, Panther, SIFT and stability of the variations was assessed by I-mutant 3.0. The proteins (native and mutant forms) coded by these genes were modeled using Swiss Model followed by validation. The mutant models and native proteins were compared for their RMSD and ASA using the tools PyMOL software and VADAR server respectively. Furthermore, BIOVIA discovery studio visualizer tool was used to visualize the presence of polymorphisms in the protein binding sites. Patchdock was used for protein - protein docking to know the effects of polymorphisms during binding. Thus, the present computational study suggest that predicted nsSNPs could possibly play a role in disease mechanism and proteins can be considered a...
Source: Meta Gene - Category: Genetics & Stem Cells Source Type: research